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Peripheral Arterial Disease: Who has it and what to do about it?
• Seth Krauss, M.D. • Alaska Annual Nurse Practitioner Conference
• September 16, 2011
Scope of the Problem
Incidence:
<5% before age 65
>20% at age 751
15% after 55
In patients with established PVD, cardiovascular mortality is
significantly increased2
> 50% prevalence of concomitant CAD
1Circulation 1985; 71: 510 2NEJM 1992; 326: 381
Overview
1. Scope of peripheral arterial disease
2. Diagnosis and management of:
• Lower extremity occlusive disease
• Renal artery stenosis
Peripheral arterial disease (PAD):
definitions
Classic: non-coronary vascular disease, usually atherosclerotic
Proposed:
a. Visceral (renal, coronary, cerebral)
b. Extremity
Once established, atherosclerosis is without organ boundary
The Ankle-Brachial Index (ABI)
• ABI measurement is the optimal method to detect PAD
– Inexpensive, accurate, and office-based
– Provides an international standard, validated by angiographic detection, for defining PAD prevalence
– Predicts limb survival, propensity for wound healing, and short- and long-term patient survival1,2
• When is an ABI measurement indicated?
– Presence or suspicion of claudication; pain at rest; or nonhealing foot ulcer
– Age >70 years or >50 years with risk factors (diabetes, smoking)
1McKenna et al. Atherosclerosis. 1991;87:119-128. 2Newman et al. JAMA. 1993;270:487-489.
How to Perform and Calculate the
ABI
Above 0.90 — Normal
0.71-0.90 — Mild Obstruction
0.41-0.70 — Moderate Obstruction
0.00-0.40 — Severe Obstruction
PARTNERS Program ABI Interpretation
Right Arm Pressure:
Left Arm Pressure:
Pressure:
PT
DP
Right ABI Higher Right Ankle Pressure mm Hg Higher Arm Pressure mm Hg
= =
Left ABI Higher Left Ankle Pressure mm Hg Higher Arm Pressure mm Hg
= = ___
Example Higher Ankle Pressure mm Hg Higher Brachial Pressure mm Hg
= 92
164 0.56 = See ABI Chart
Pressure:
PT
DP
____
New Criteria
1.10-1.4 – Normal
1.0-1.09 – Low Normal
0.90-0.99 – Borderline Abnl
ABI: Limitations
• Possible false negatives in patients with noncompressible arteries, such as elderly and diabetic individuals
• ABI NEW NORMAL 1.1-1.39
– BORDERLINE ABNL 0.91-0.99
– LOW NORMAL 1.0-1.09
• Insensitive to very mild occlusive disease or iliac occlusive disease
• Poor correlation with functional status in patients with claudication, therefore should be used in conjunction with standardized patient questionnaires to assess PAD severity
10 year all-cause mortality in PAD patients
0
25
50
75
100
0 2 4 6 8 10
year
Su
rviv
al
Normal
Asymptomatic PAD
Symptomatic PAD
Severely symptomatic PAD
0
20
40
60
80
100
Mortality in Patients
With Severe PAD
Relative 5-Year Mortality
1McKenna M et al. Atherosclerosis. 1991;87:119-128. 2Ries LAG et al. SEER Cancer Statistics Review, 1973-1997. National Cancer Institute.
Pati
en
ts (
%)
15
38 44
48
Colon/Rectal Cancer2
Non- Hodgkin’s
Lymphoma2
Breast Cancer2
PAD1
3434
Atherosclerotic Diseases in the PARTNERS Study Population
Atherosclerotic Diseases in the PARTNERS Study Population
*Cardiovascular disease defined as individuals with clinical evidence of coronary artery or cerebral arterial atherosclerotic syndromes.
*Cardiovascular disease defined as individuals with clinical evidence of coronary artery or cerebral arterial atherosclerotic syndromes.
PAD+/CVD-PAD+/CVD-
Peripheralarterialdisease
only
Peripheralarterialdisease
only
PAD+/CVD+PAD+/CVD+
Peripheralarterial disease
andcardiovascular
disease
Peripheralarterial disease
andcardiovascular
disease
PAD-/CVD+PAD-/CVD+
Cardiovasculardisease*
only
Cardiovasculardisease*
only
PAD-/CVD-PAD-/CVD-
“Healthy Adults”No evident
atherosclerosis
“Healthy Adults”No evident
atherosclerosis
PARTNERS provided an opportunity to compare data betweenfour relevant community-derived populations
PARTNERS provided an opportunity to compare data betweenfour relevant community-derived populations
3636
Inclusion and Exclusion CriteriaInclusion and Exclusion Criteria
Targeted populations with atherosclerotic risk factors
Age (>70 years)
Younger individuals (50-69 years) with risk factors (smoking, diabetes)
Geographically diverse sample
Study centers in major urban regions ofthe US
Initial Target Sample Size
Goal: 1,500 PAD subjects by screening 10,000 “at risk” individuals
Targeted populations with atherosclerotic risk factors
Age (>70 years)
Younger individuals (50-69 years) with risk factors (smoking, diabetes)
Geographically diverse sample
Study centers in major urban regions ofthe US
Initial Target Sample Size
Goal: 1,500 PAD subjects by screening 10,000 “at risk” individuals
4444
0
20
40
60
80
100PAD+/CVD-
PAD-/CVD+
PAD+/CVD+
PAD-/CVD-
0
20
40
60
80
100PAD+/CVD-
PAD-/CVD+
PAD+/CVD+
PAD-/CVD-
WalkingDistance
WalkingDistance
WalkingSpeed
WalkingSpeed
WIQ Measures of Walking Distance and Speed Across Diagnostic Groups
WIQ Measures of Walking Distance and Speed Across Diagnostic Groups
WIQ
Score
WIQ
Score
WIQ
Score
n=313 n=376 n=205 n=1,168 n=339 n=383 n=207 n=1,201n=313 n=376 n=205 n=1,168 n=339 n=383 n=207 n=1,201
PARTNERS Preliminary Data Report.PARTNERS Preliminary Data Report.
4848
Physician Awareness of PAD by Individual Patient PAD/CVD Status
Physician Awareness of PAD by Individual Patient PAD/CVD Status
*P<.001
PARTNERS Preliminary Data Report.
*P<.001
PARTNERS Preliminary Data Report.
% P
hysic
ian
sA
ware o
f P
AD
% P
hysic
ian
sA
ware o
f P
AD
0
20
40
60
80
100
Reportedly Aware of PAD
Reportedly Unaware of PAD
0
20
40
60
80
100
Reportedly Aware of PAD
Reportedly Unaware of PAD
28.7%28.7%
71.3%71.3%
22.8%22.8%
77.2%77.2%
38.1%38.1%
61.9%61.9%
n=564
All With PAD
n=564
All With PAD
n=346
With PADOnly*
n=346
With PADOnly*
n=218
WithPAD & CVD*
n=218
WithPAD & CVD*
4949
Physician Awareness of PADPhysician Awareness of PAD
0
10
20
30
40
50
All With PAD With PAD Only With PAD & CVD
0
10
20
30
40
50
All With PAD With PAD Only With PAD & CVD
% M
D A
waren
ess
% M
D A
waren
ess
Smoking and diabetesSmoking and diabetes
>70 years>70 years
28.0%28.0%
35.8%35.8%
29.3%29.3%
23.0%23.0%
46.2%46.2%
35.4%35.4%
PARTNERS Preliminary Data Report.PARTNERS Preliminary Data Report.
5050
n=564
All With PAD
n=564
All With PAD
n=346
With PADOnly*
n=346
With PADOnly*
n=218
WithPAD & CVD*
n=218
WithPAD & CVD*
% S
ub
jects
% S
ub
jects
0
20
40
60
80
100
Reportedly Aware of PAD
Reportedly Unaware of PAD
0
20
40
60
80
100
Reportedly Aware of PAD
Reportedly Unaware of PAD
Patient Awareness of PAD by PAD/CVD Status
Patient Awareness of PAD by PAD/CVD Status
*P<.001.
PARTNERS Preliminary Data Report.
*P<.001.
PARTNERS Preliminary Data Report.
48.8%48.8% 51.2%51.2%
42.8%42.8%
57.2%57.2% 58.3%58.3%
41.7%41.7%
Lower-extremity: symptom generation
asymptomatic
claudication
rest-pain
limb-threat 2-level
1-level
Iliac (in-flow)
Superficial femoral artery
(outflow)
Popliteal
Tibioperoneal
(run-off)
Claudication - Natural History
• Symptoms remain stable or improve with time in 65% - 70% of
patients due to development of collateral vessels.
• < 25% ever need surgery or angioplasty.
• Low risk of losing a limb - only 1.4% per year progress to critical
life-threatening ischemia (however, patients with diabetes have an
increased overall amputation risk of 20%).
Lower-extremity ischemia:
therapeutics Medical
Risk factor modification
Exercise
Supervised; 6 mos.
Tobacco cessation
Cilostazol
PDE-III inhibitor
1-2 month trial
drug interaction
L-arginine
Lower-extremity ischemia: therapeutics
Endovascular Stents:
Improved iliac patency/durability c/w angioplasty
Below inguinal ligament application less clear, but suggestive
Stent-grafts:
Attempt at improving restenosis rates, aneurysmal disease
Total occlusion devices:
Attempt to improve success in long occlusions in iliac/SFA
Angiogenesis:
IM injection of VEGF resulting in increased collateral flow
Radiation:
PARIS trial using gamma radiation
Lower-extremity ischemia: therapeutics
Femoropopliteal Disease
Surgical Option
Indicated for severe lifestyle-limiting
claudication and long occlusions.
5 year patency rate for vein grafts
Graft Type Fem-pop Tibial
autologous 75% 67%
synthetic 50% 14%
Femoropopliteal Disease
Surgical Option
• operative mortality 1.7 - 3.5%
• operative morbidity 10%
• hospital stay 4-7 days
• resumption of full activity 4 weeks
• need for CABG?
Infrainguinal Disease: Ideal Candidates
Surgery
Clinical
– < 70 year old
– Non-diabetic
Anatomic
– Single segment with intact
run-off
– Long SFA stenosis
– Multi-segment disease with
intact run-off
– Lesions Causing
Atheroembolism
Percutaneous
Clinical – non-diabetic, absence of
gangrene
Anatomic
– Short
– Non-calcified
– Non total occlusion
– Run-off intact
– Adjacent Aneurysmal
Segment
– Bail-out
Lower-extremity
Indications for revascularization are
evolving…
asymptomatic
claudication
rest-pain
limb-threat
2-level
1-level
When did you last make the diagnosis?
Renal artery stenosis
Renovascular disease: incidence 1%-5% in general, but more in selected
populations:
Iliofemoral arterial disease: 30%-40%
Carotid disease: 20%-30%
Coronary artery disease: 20%-30%
Congestive heart failure: 30%
ESRD: 20%
80% atherosclerotic/20% fibromuscular dysplasia
In general, the severity of associated atherosclerotic disease correlates with renal artery stenosis severity
Renovascular disease:
pathophysiology Hypertension
Renal parenchymal hypoperfusion with activation of the renin-angiotensin-aldosterone system
Vasoconstriction
Aldosterone-mediated volume expansion
Endothelial dysfunction (chronic changes)
Modulated by contralateral kidney naturesis and ipsilateral capsular collaterals
Renal insufficiency
Ipsilateral chronic hypoperfusion and progressive “ischemic nephropathy”
Contralateral hypertensive arteriolar nephrosclerosis with “Hyperfiltration”
Cholesterol/atheromatous embolization
Renovascular disease: natural history
Progressive disease
Baseline severity predicts progression:
Normal~5%/year
<60% stenosis~10%/year
>60% stenosis~15%/year
Occlusion: ~3%-5%/year
Worse in high-grade lesions, diabetics
Independent predictor of mortality
10% excess 5 and 10 year mortality in patients with hypertension and RAS
Renovascular disease: predictors
Onset of hypertension <25 or >55 years old
Recent or abrupt onset, or worsening/resistant hypertension (> 2 medications)
Unexplained azotemia
Abdominal bruit
ACEI-induced renal dysfunction (bilateral RAS)
Recurrent pulmonary edema and hypertension
Marked difference in renal size
Diabetes
Renovascular disease: evaluation
Non-invasive testing for at-risk
patients:
No non-invasive “gold-standard”
Characterized as
functional (renin-angiotensin axis)
anatomic (imaging/hemodynamic data)
Renovascular disease:anatomic testing
Doppler ultrasound
Operator dependent/~80% technically feasible
Sensitivity~90% Specificity~95%
High negative/positive predictive value, except in patients with accessory renal arteries (20%-30% incidence)
Graded 0%, <60%, >60% stenosis
MR angiogram
Gadolinium enhancement improves imaging
Some patients cannot be tested
Expensive
CT angiogram
Contrast exposure
Expensive
Renovascular disease:medical therapy
In unilateral disease, ACEI and ARB’s are safe and effective
Beta-blockers are also effective
Medications usually effective in controlling hypertension associated with RAS
However, renal size and GFR continue to decrease even with good hypertensive control
Compared with surgery, long-term mortality with medical therapy is worse
Renovascular disease:percutaneous Rx
Angioplasty alone
Limited by suboptimal acute (<80%) and long-term success rates (restenosis 20%-25%)
Stent
Good acute (>95%)and long-term (~85%) success rates
Complication rate of 5%-10%
Hemorrhage, embolism, renal failure
Mortality~1%
Efficacy
Improved hypertension in 2/3 (cure 10%)
Stabilized or improved renal function in 2/3
No randomized trial data available
Improved CHF and coronary ischemia control
PAD: Summary
• LE PAD Common • Marker for IHD, Cerebrovascular Dz – correlate for
ischemic burden
• Under Diagnosed – PARTNERS
• ABI – powerful prognostic cardiovascular
test – Serial study if ABI 0.90-1.09
• Treatment • Goals to increase functionality & quality of life
• Secondary prevention
PAD: Summary Renal
• Renal Artery Stenosis • Consider in Refractory Hypertensive patient
• Worsening renal function
• Renal assymetry
• Recurrent CHF
• Screen with Renal Duplex
• Selective intervention
– HTN
– Ischemic nephropathy
– CHF